Melatonin suppresses autophagy in type 2 diabetic osteoporosis
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Wei-Lin Zhang1,*, Hong-Zheng Meng1,*, Rui-Fei Yang2,*, Mao-Wei Yang1, Guang-Hong Sun1, Jun-Hua Liu1, Peng-Xu Shi1, Fei Liu1, Bo Yang1
1Department of Orthopedics, the First Hospital of China Medical University, Shenyang, Liaoning, China
2School of Medical Applied Technology, Shenyang Medical College, Shenyang, Liaoning, China
*These authors have contributed equally to this work
Mao-Wei Yang, email: [email protected]
Keywords: melatonin, type 2 diabetes osteoporosis, osteoblast, autophagy, ERK
Received: February 11, 2016 Accepted: June 30, 2016 Published: July 11, 2016
Type 2 diabetes mellitus is often complicated by osteoporosis, a process which may involve osteoblast autophagy. As melatonin suppresses autophagy under certain conditions, we its investigated the effects on bone autophagy during diabetes. We first assessed different body parameters in a diabetic rat model treated with various concentrations of melatonin. Dynamic biomechanicalmeasurements, bone organization hard slice dyeing and micro-CT were used to observe the rat bone microstructure, and immunohistochemistry was used to determine levels of autophagy biomarkers. We also performed in vitro experiments on human fetal osteoblastic (hFOB1.19) cells cultured with high glucose, different concentrations of melatonin, and ERK pathway inhibitors. And we used Western blotting and immunofluorescence to measure the extent of osteogenesis and autophagy. We found that melatonin improved the bone microstructure in our rat diabetes model and reduced the level of autophagy(50 mg/kg was better than 100 mg/kg). Melatonin also enhanced osteogenesis and suppressed autophagy in osteoblasts cultured at high glucose levels (10 μM was better than 1 mM). This suggests melatonin may reduce the level of autophagy in osteoblasts and delay diabetes-induced osteoporosis by inhibiting the ERK signaling pathway.
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